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New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft‐versus‐host disease
Author(s) -
Lutz Mathias,
Mielke Stephan
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13022
Subject(s) - everolimus , sirolimus , transplantation , medicine , stem cell , haematopoiesis , pi3k/akt/mtor pathway , hematopoietic stem cell transplantation , immunology , pharmacology , oncology , biology , apoptosis , biochemistry , genetics
Inhibition of the mechanistic target of rapamycin (mTOR) has been exploited largely both in solid tumour oncology and solid organ transplantation. More recently mTOR inhibitors such as sirolimus and everolimus have been introduced to the field of allogeneic haematopoietic stem cell transplantation where their unique combination of immunosuppressive purposes offering reduced nephrotoxicity and potential antimalignant effects reflect a unique drug profile that has led to their widespread use in both prophylaxis and therapy of graft‐versus‐host disease (GVHD). On the other hand haematological insufficiency, infectious complications as well as vasculopathies, have been frequently reported as limiting toxicities. Here, we review both the retrospective and prospective experience available to date and stress the need for prospective registration trials to reduce off label use and improve patient safety by optimizing dosing and enhancing pharmacovigilance. Furthermore, we speculate on the future role of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation.